C-Reactive protein (CRP) and serum amyloid P component (SAP) are two closely related proteins with respect to their primary structure and their pentameric appearance under the electron microscope. The two proteins have unknown functions. A common property shared by CRP and SAP is their ability to bind to sulfated polysaccharides and to fibronectin in a calcium-dependent manner. Using techniques including cell attachment assays, tissue culture, peptide synthesis and immunoassay, a peptide modeled after the primary sequence of SAP was found to bind strongly and specifically to heparin and certain other sulfated polysaccharides. This binding was independent of calcium. The homologous peptide from CRP also bound heparin. Using capillary zone electrophoresis we were able to demonstrate for the first time the binding of a small peptide, F-T-L-C-F- R tp a simple sugar, mannose-6-phosphate. This interaction occurs at any pH and is dependent of divalent cations such as Ca2+ Both, SAP and CRP will bind to heparin-Sepharose at pH 5.5, the pH of tissue during inflammation. This pH is independent of Ca2+ and clearly parallels the synthetic peptide. This finding points to a role for the CRP-heparin complex during inflammation at lower pH values where CRP was previously shown to activate serum complement. In addition, the ability to bind DNA and activate complement at low pH might be indicative of a role played by CRP in the transfer of genetic material during tissue destruction. Combined, these results point to a more complete understanding of the acute of the acute phase response. Such knowledge will be useful in developing therapeutics and vaccines whose unknown side effects include the induction of the acute phase response. GRANT=Z01DE00434 HIV -1 is the causative agent of AIDS. CD4 is the cellular receptor for HIV-1 and its amino acid sequence is known. The region of HIV-1 that binds to CD-4 is termed gp160 and this is the envelope glycoprotein that is composed of gp120 and gp41. The gp120 region specifically binds to CD4 and the sequences of amino acids in both CD4 and gp120 that are responsible for the high affinity binding of the virus are now known. Prior to this report, it was believed that the binding site for gp120 on CD-4 could not be chemically synthesized. The reason for this is that the binding site is believed to be conformationally constrained. We have synthesized a peptomer from amino acids 419-436 of the gp120 from the MN isolate of HIV-1 and we have learned that, by specifically polymerizing peptide (419-436) we enhance the `-helical conformation of the peptide. With peptomer (419-436), we have learned the following: First, 96% of the patients suffering from HIV-1 infection have antibodies to this region of gp 120 and these antibodies are able to neutralize HIV- 1 infection in vitro. Second, peptomer (419-436) binds CD4 and this binding inhibits human antibodies from binding peptomer (419-436). In addition, CD4-expressing cells such as CEM and MOLT-3 bind peptomer (419- 436). Third, rabbit antibodies produced in Freund's adjuvant against peptomer (419-436) do not recognize gp120 or neutralize HIV-1 infection in vitro. However, rabbit antibodies produced in Ribi's adjuvant do recognize gp120 and they do neutralize HIV-1 infection in vitro. These results indicate that the binding of HIV-1 to CD4 is conformation-dependent and future therapeutics and vaccines that target this binding must be developed with conserved conformational constraints.